This application proposes experimentation designed to identify the cell and cellular mechanism responsible for bone resorption during tumor osteolysis. Tumor osteolysis occurs when primary or metastatic malignancies are present in bone and cause bone destruction. Clinically, this process results in pain, decreased mobility, hypercalcemia, anemia and skeletal fracture. Deficiencies in prevention, early detection and treatment underscore the fact that knowledge defining the biology of tumor osteolysis is scarce. Specifically neither the cell nor the cellular mechanism responsible for tumor osteolysis has been identified. Research proposed within this application is designed to identifying the cell and cellular mechanism which are responsible for bone resorption during tumor osteolysis. The experimentation which is proposed will 1) study tumor osteolysis with an in vivo murine model, 2) study tumor osteolysis with an in vitro murine model, and 3) study tumor osteolysis from human tumor cells in vivo (using athymic mice) and in vitro.